WO2023234485A1 - Biomarqueur pour prédire la probabilité de développer un cancer gastrique et son utilisation - Google Patents

Biomarqueur pour prédire la probabilité de développer un cancer gastrique et son utilisation Download PDF

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WO2023234485A1
WO2023234485A1 PCT/KR2022/014463 KR2022014463W WO2023234485A1 WO 2023234485 A1 WO2023234485 A1 WO 2023234485A1 KR 2022014463 W KR2022014463 W KR 2022014463W WO 2023234485 A1 WO2023234485 A1 WO 2023234485A1
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gastric cancer
level
predicting
mrna
developing
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PCT/KR2022/014463
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Korean (ko)
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조수정
김상균
박미리
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서울대학교병원
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer

Definitions

  • the present invention relates to biomarkers for predicting the possibility of developing gastric cancer and their use.
  • stomach cancer is the second leading cause of cancer-related death worldwide regardless of gender, and is a common cause of death. It remains one of the causes.
  • the exact mechanism underlying the most important gastric cancer development and tumor progression has not yet been fully elucidated.
  • the reason Korea has the highest incidence of stomach cancer in the world is because underlying gastritis has progressed to a large extent.
  • Metachronous Gastric Cancer refers to a case discovered 12 months after gastric cancer was diagnosed. Specifically, gastric cancer that newly develops in a site other than the original treatment site during follow-up after gastric cancer was treated with endoscopic resection. Examples include:
  • the present inventor confirmed that the expression level of CDK1 and KDF1 measured in normal mucosa other than gastric cancer at the time of endoscopic submucosal dissection for early gastric cancer can be used to predict the development of metachronous gastric cancer in the future, and that the CREB5 and AKT2 isoform genes
  • the present invention was completed by confirming that not only metachronous gastric cancer but also gastric cancer occurrence can be predicted in normal people through one-time gene expression measurement in a single tissue sample.
  • CDK1, KDF1, CREB5, and AKT2 isoform genes of the present invention Through the expression patterns of the CDK1, KDF1, CREB5, and AKT2 isoform genes of the present invention, an individualized approach to observing the development of metachronous gastric cancer in the future will be possible through risk stratification for patients who have undergone endoscopic submucosal dissection for early gastric cancer. In addition, it provides a quantitative method that can predict the occurrence of stomach cancer even in normal people, and it provides a method to predict the occurrence of stomach cancer in normal people with a family history of stomach cancer or risk factors.
  • the purpose of the present invention is to provide a composition for predicting the possibility of developing gastric cancer, which includes an agent for measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CREB5 and AKT2.
  • Another object of the present invention is to provide a kit for predicting the possibility of developing stomach cancer, including the composition.
  • Another object of the present invention is a composition for predicting the possibility of developing metachronous gastric cancer, comprising an agent for measuring the level of mRNA or protein expressed therefrom of any one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2.
  • a composition for predicting the prognosis of early gastric cancer patients treated with endoscopic submucosal dissection is provided.
  • Another object of the present invention is to provide a method for providing information for predicting the possibility of developing gastric cancer, which includes measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CREB5 and AKT2. will be.
  • Another object of the present invention is to predict the possibility of developing metachronous gastric cancer, which includes measuring the level of mRNA or protein expressed therefrom of any one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2.
  • the goal is to provide a method of providing information for or predicting the prognosis of patients with early gastric cancer after endoscopic submucosal dissection treatment.
  • the present invention provides a composition for predicting the possibility of developing gastric cancer, comprising an agent for measuring the level of mRNA or protein expressed therefrom of any one or more genes selected from the group consisting of CREB5 and AKT2. to provide.
  • the stomach cancer may include, but is not limited to, metachronous stomach cancer.
  • the composition may further include, but is not limited to, an agent for measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CDK1 and KDF1.
  • the agent for measuring the mRNA level of the gene may be a primer or probe that specifically binds to the gene or mRNA, but is not limited thereto.
  • the agent for measuring the level of the protein may be an antibody or aptamer specific for the protein, but is not limited thereto.
  • the present invention provides a kit for predicting the likelihood of developing stomach cancer, including the composition.
  • the kit includes a reverse transcription polymerase chain reaction (RT-PCR) kit, a real-time polymerase chain reaction (qRT-PCR) kit, a DNA chip kit, an enzyme-linked immunosorbent assay (ELISA) kit, and It may be one or more selected from the group consisting of protein chip kits, but is not limited thereto.
  • RT-PCR reverse transcription polymerase chain reaction
  • qRT-PCR real-time polymerase chain reaction
  • DNA chip kit e.g., a DNA chip kits
  • ELISA enzyme-linked immunosorbent assay
  • the present invention provides a composition for predicting the possibility of developing metachronous gastric cancer, comprising an agent for measuring the level of mRNA or protein expressed therefrom of any one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2. to provide.
  • the present invention relates to early gastric cancer patients treated with endoscopic submucosal dissection, comprising an agent for measuring the level of mRNA or protein expressed therefrom of any one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2.
  • an agent for measuring the level of mRNA or protein expressed therefrom of any one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2. Provides a composition for predicting prognosis.
  • the present invention includes the steps of (a) measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CREB5 and AKT2 in a biological sample isolated from a subject; and
  • the gastric cancer may include metachronous gastric cancer, and the method includes mRNA or expression of one or more genes selected from the group consisting of CDK1 and KDF1 in a biological sample isolated from a subject. It may further include, but is not limited to, measuring the level of the protein and comparing it with the level measured in a sample separated from the control group.
  • the mRNA level of the gene is determined by reverse transcription polymerase chain reaction (RT-PCR), competitive reverse transcription polymerase chain reaction (competitive RT-PCR), real time quantitative RT- PCR), multiplex reverse transcription polymerase chain reaction (Multi-plex PCR), real-time polymerase chain reaction (qRT-PCR), RNase protection method, Northern blotting, DNA chip analysis method (DNA chip technology assay), methylated DNA binding domain sequencing (MBD-seq) analysis method, and reduced representation bisulfite sequencing (RRBS) analysis method. It can be measured by, but is not limited to.
  • the protein level is measured by Western blot, enzyme linked immunosorbent assay (ELISA), radioimmunoassay (RIA), radioimmunodiffusion, or ucterolysis.
  • ELISA enzyme linked immunosorbent assay
  • RIA radioimmunoassay
  • ucterolysis Ouchterlony immunodiffusion method, rocket immunoelectrophoresis, immunohistochemistry (IHC), immunoprecipitation assay, complement fixation assay, flow cytometry (Fluorescence Activated Cell Sorter, It may be measured by one or more methods selected from the group consisting of FACS), and protein chip, but is not limited thereto.
  • the mRNA level or protein level of the gene may be measured using a single biological sample, but is not limited thereto.
  • the biological sample may be one or more selected from the group consisting of tissue, cells, whole blood, serum, plasma, saliva, sputum, cerebrospinal fluid, urine, and feces isolated from the subject, but Not limited.
  • the method may (c) increase the risk of developing gastric cancer when the level of the mRNA or protein measured in a biological sample isolated from a subject is higher than the level measured in a biological sample isolated from a control group; It may further include a step of determining that the level is high, but is not limited thereto.
  • the present invention includes the steps of (a) measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2 in a biological sample isolated from a subject; and
  • the present invention provides the step of (a) measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2 in a biological sample isolated from an early gastric cancer patient. ; and
  • the present invention includes the steps of (a) measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CREB5 and AKT2 in a biological sample isolated from a subject; and
  • the present invention includes the steps of (a) measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2 in a biological sample isolated from a subject; and
  • the present invention provides the step of (a) measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2 in a biological sample isolated from an early gastric cancer patient. ; and
  • the present invention provides a use for predicting the possibility of developing gastric cancer of a composition
  • a composition comprising an agent for measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CREB5 and AKT2.
  • the present invention provides the use of an agent for measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CREB5 and AKT2 for preparing an agent for predicting the possibility of developing gastric cancer.
  • the present invention provides a use for predicting the possibility of developing metachronous gastric cancer of a composition comprising an agent for measuring the level of mRNA or protein expressed therefrom of any one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2. to provide.
  • the present invention provides an agent for measuring the level of mRNA or protein expressed therefrom of any one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2 for producing an agent for predicting the possibility of developing metachronous gastric cancer. Provides a purpose.
  • the present invention provides an early stage treated with endoscopic submucosal dissection of a composition comprising an agent for measuring the level of mRNA or protein expressed therefrom of any one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2. It is used to predict the prognosis of stomach cancer patients.
  • the present invention provides the mRNA of one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2 or the protein expressed therefrom for producing an agent for predicting the prognosis of patients with early gastric cancer treated with endoscopic submucosal dissection. Provides the use of preparations to measure levels.
  • the composition for predicting the possibility of developing stomach cancer according to the present invention not only has high accuracy in predicting the occurrence of stomach cancer, but also allows prediction of stomach cancer with a single measurement method by using multi-plex PCR, etc. with a single tissue sample, so it is useful. high.
  • it since it includes a method to quantify basal gastritis in a quantitative way that can predict the development of gastric cancer as well as metachronous gastric cancer, it provides a method to predict the risk of developing gastric cancer even in normal people with a family history of gastric cancer or risk factors.
  • it has the effect of predicting the patient's prognosis by predicting the onset of metachronous gastric cancer in patients with early gastric cancer treated with endoscopic submucosal dissection.
  • Figures 1a to 1e show the results of DESeq2 analysis of normal gastric mucosal tissue around the tumor, respectively, and the results of correlation analysis according to gene expression level, number of gastric cancers, number of adenomas, atrophic gastritis (OLGA stage), and degree of intestinal metaplasia (OLGMI stage).
  • Figure 1a the result showing the expression level of CDK1 among the candidate genes confirmed to be highly expressed in the metachronous gastric cancer group ( Figure 1b), the result of confirming the self-organizing map (SOM) ( Figure 1c), alternative The results of splicing (Altearnative splicing analysis) analysis ( Figure 1d) and the cDNA sequence and amino acid sequence of the AKT2 isoform set as the target ( Figure 1e) are shown.
  • Figure 2 shows the results of selecting candidate genes as metachronous gastric cancer biomarkers considering the results of bulk RNA sequencing analysis performed on normal gastric mucosa tissue.
  • Figure 3 shows the results of evaluating cell viability in gastric cancer cell lines treated with siRNA.
  • Figure 4a shows the effectiveness evaluation results of CDK1, KDF1, POLR2L, CREB5, and AKT2-isoform gene expression.
  • Figure 4b shows the results of Western blot confirmation of CDK1 and KDF1 protein expression levels in normal gastric mucosal tissue (control) around the tumor and patient tissue (mGC) with metachronous gastric cancer.
  • Figure 4c shows the results of confirming the level of CDK1 protein expression in normal gastric mucosa tissue (control) around the tumor and tissue (mGC) of a patient with metachronous gastric cancer using immunohistochemistry.
  • Figure 4d shows the results of confirming the level of KDF1 protein expression in normal gastric mucosa tissue (control) around the tumor and tissue (mGC) of a patient with metachronous gastric cancer using immunohistochemistry.
  • Figures 5a to 5d are the results of ROC curve analysis of CDK1, KDF1, CREB5, and AKT2-isoform genes and prediction of gastric cancer occurrence.
  • Figure 6 shows the results showing CREB5 gene expression according to OLGIM stage.
  • Figure 7 shows the results showing AKT2 gene expression according to OLGIM stage.
  • normal gastric mucosal tissue at the time of diagnosis was obtained and stored in patients with early gastric cancer treated with endoscopic submucosal dissection, between patients who developed metachronous gastric cancer and patients who did not develop metachronous gastric cancer during follow-up.
  • Differentially expressed genes were identified, and correlation analysis was conducted according to the gene expression level, number of metachronous gastric cancers, number of adenomas, atrophic gastritis (OLGA stage), and degree of intestinal metaplasia (OLGIM stage).
  • CDK1, KDF1, ERCC6L, KLK8, MCM2, POLR2L, PTN, CREB5, and AKT2-isoform were selected as candidate genes by performing self organizing map (SOM) analysis and isoform analysis. See example 1).
  • the accuracy of each genetic marker for predicting metachronous gastric cancer was high, especially the CDK1, KDF1, and AKT2-isoform genes. It was confirmed that accuracy increased the most when isoform markers were combined. In addition, it was confirmed that CREB5 and AKT2 isoforms show expression differences depending on OLGIM stage, confirming that prediction of gastric cancer is possible not only in metachronous gastric cancer but also in normal people with a family history of gastric cancer or risk factors (see Example 3).
  • the present invention provides a composition for predicting the possibility of developing gastric cancer, comprising an agent for measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CREB5 and AKT2.
  • the composition may further include an agent for measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CDK1 and KDF1, but is not limited thereto.
  • the present invention provides a composition for predicting the possibility of developing metachronous gastric cancer, comprising an agent for measuring the level of mRNA or protein expressed therefrom of any one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2. to provide.
  • composition may contain one gene among the four genes or a combination of two, three, or four genes.
  • CREB5 is a gene highly associated with the OLGIM stage and does not show a significant correlation with mGC itself compared to other genes, but AKT2-isoform is a gene highly associated with the OLGIM stage.
  • AKT2-isoform is a gene highly associated with the OLGIM stage.
  • CDK1, KDF1, and AKT2-isoform may be the most accurate in predicting the possibility of developing metachronous gastric cancer.
  • it is limited to the combination of the above genes. That is not the case.
  • the composition of the present invention can obtain useful information for predicting the possibility of developing gastric cancer by measuring when the expression of the above gene increases. This has not been known until now, and was discovered for the first time by the present invention, leading to early gastric cancer. For patients who have undergone endoscopic submucosal dissection, not only is it possible to observe the development of metachronous gastric cancer in the future, it is also possible to predict the prognosis, and as a quantitative method to predict the possibility of developing gastric cancer even in normal people, multi-plex analysis of a single tissue sample is performed. It is significant in that it is possible to predict stomach cancer with a single measurement method using PCR.
  • CDK1 Cyclin Dependent Kinase 1
  • cyclin-dependent kinase 1 also known as cell division cycle protein 2 homolog
  • the CDK1 may include the amino acid sequence (SEQ ID NO: 1) of NCBI Reference Sequence: NP_001777.1, and may be encoded by the nucleotide sequence (SEQ ID NO: 2) of NCBI Reference Sequence: NM_001786.5, but is not limited thereto. No.
  • KDF1 Keratinocyte Differentiation Factor 1
  • the KDF1 may include the amino acid sequence (SEQ ID NO: 3) of NCBI Reference Sequence: NP_689578.2, and may be encoded by the nucleotide sequence (SEQ ID NO: 4) of NCBI Reference Sequence: NM_152365.3, but is not limited thereto. No.
  • CREB5 cAMP responsive element binding protein 5
  • the CREB5 may include the amino acid sequence (SEQ ID NO: 5) of NCBI Reference Sequence: NP_878901.2, and may be encoded by the nucleotide sequence (SEQ ID NO: 6) of NCBI Reference Sequence: NM_182898.4, but is not limited thereto. No.
  • CREB5 increases as the stage increases in the OLGIM (Operative Link on Gastritis Assessment based on Intestinal Metaplasia) system, which is based on intestinal metaplasia, especially in gastric cancer. It was confirmed that the expression level of CREB5 was significantly increased in stages 3 and 4, which are high-risk groups, and that it was possible to predict the possibility of developing gastric cancer.
  • OLGIM Oxperative Link on Gastritis Assessment based on Intestinal Metaplasia
  • AKT2 (AKT Serine/Threonine Kinase 2, RAC-beta serine/threonine-protein kinase) plays a very important role as a mediator in the signaling pathway downstream of activated tyrosine kinase and PI3K.
  • the cellular functions regulated by AKT include cell proliferation, cell survival, cell size control, responsiveness to available nutrients, intermediary metabolic processes, angiogenesis, and tissue invasion, which influence the role of cellular functions. It is known that Specifically, AKT2 of the present invention may refer to an AKT2 isoform, but is not limited thereto.
  • the AKT2 isoform may include the amino acid sequence of SEQ ID NO: 7 and may be encoded by the base sequence of SEQ ID NO: 8, but is not limited thereto.
  • the expression of the AKT2 isoform protein was significantly increased in the patient group with a high OLGIM stage compared to the patient group with a low OLGIM stage, indicating that it can be used to predict the possibility of developing gastric cancer. Confirmed.
  • agent for measuring the level of mRNA refers to an agent used in a method for measuring the level of mRNA transcribed from a gene of the present invention contained in a sample in order to determine whether the gene is expressed. .
  • the agent for measuring the mRNA level of the gene may be a primer or probe that specifically binds to the gene or mRNA, but is not limited thereto.
  • a “primer” is a short single strand oligonucleotide that acts as a starting point for DNA synthesis.
  • the primer binds specifically to the polynucleotide as a template under appropriate buffer and temperature conditions, and DNA polymerase adds a nucleoside triphosphate with a base complementary to the template DNA to the primer and connects it to the DNA. is synthesized.
  • Primers generally consist of 15 to 30 base sequences, and the melting temperature (Tm) at which they bind to the template strand varies depending on base composition and length.
  • the sequence of the primer does not need to be completely complementary to some of the base sequences of the template, but it is sufficient as long as it has a length and complementarity suitable for the purpose of measuring the amount of mRNA by amplifying a specific section of mRNA or cDNA through DNA synthesis. do. Therefore, in the present invention, a primer pair can be easily designed by referring to the base sequence of the cDNA or genomic DNA of the gene or its mRNA.
  • Primers for the amplification reaction consist of a set (pair) that binds complementary to the template (or sense) and the opposite side (antisense) at both ends of a specific section of the mRNA to be amplified.
  • probe refers to RNA or DNA with a length of several to hundreds of base pairs that can specifically bind to mRNA, cDNA (complementary DNA), or DNA of a specific gene. It refers to a fragment of a polynucleotide, and is labeled so that the presence or absence and expression level of the target mRNA or cDNA to which it binds can be confirmed. Probe selection and hybridization conditions can be appropriately selected according to techniques known in the art.
  • the probe can be used in a diagnostic method to detect an allele (or allele).
  • the diagnostic method includes detection methods based on hybridization of nucleic acids such as Southern blot, and in the method using a DNA chip, it may be provided in a form pre-bound to the substrate of the DNA chip.
  • primers or probes can be chemically synthesized using phosphoramidite solid support synthesis or other well-known methods. Additionally, primers or probes can be modified in various ways according to methods known in the art to the extent that they do not interfere with hybridization with the polynucleotide that is the target to be detected. Examples of such modifications include methylation, capping, substitution of a native nucleotide with one or more homologs, and modifications between nucleotides, such as uncharged linkages (e.g., methyl phosphonates, phosphotriesters, phosphoroamidates, carbamates, etc.) ) or charged linkers (e.g. phosphorothioate, phosphorodithioate, etc.), and binding of labeling material using fluorescence or enzymes.
  • uncharged linkages e.g., methyl phosphonates, phosphotriesters, phosphoroamidates, carbamates, etc.
  • charged linkers e.g. phosphorothi
  • the primer or probe is not limited to a specific sequence as long as it can detect the gene or its mRNA.
  • the agent for measuring the level of the protein may be an antibody or aptamer specific for the protein, but is not limited thereto.
  • aptamer refers to a single-stranded nucleic acid (DNA, RNA or modified nucleic acid) that has a stable tertiary structure and has the characteristics of being able to bind to a target molecule with high affinity and specificity.
  • Aptamers for various target substances proteins, sugars, dyes, DNA, metal ions, cells, etc.
  • SELEX Systematic Evolution of Ligands of Exponential enrichment
  • antibody refers to a protein molecule that is directed to an antigenic site and binds specifically.
  • Antibodies can be produced by methods commonly practiced in the art, such as fusion methods, recombinant DNA methods, or phage antibody library methods.
  • the antibody or fragment of an antibody may be derived from a different organism, including a human, mouse, rat, hamster, rabbit, or camel, such as a monoclonal or polyclonal antibody, immunologically active fragment, antibody, etc. It may be a heavy chain, a humanized antibody, an antibody light chain, a genetically engineered single chain F ⁇ molecule, or a chimeric antibody.
  • the antibody is not limited to a specific type of antibody as long as it can detect the protein of the present invention.
  • gastric cancer refers to all cancers that occur in the stomach.
  • Gastric adenocarcinoma which accounts for most of gastric cancer, arises from glandular cells of the gastric mucosa and is divided into several types depending on the shape observed under a microscope. It can be shared.
  • lymphoma arising from lymphoid tissue, interstitial tumor arising from stomach nerve and muscle tissue, sarcoma (malignant tumor originating from non-epithelial tissue), and neuroendocrine cancer that secretes hormones are all included in gastric cancer. You can.
  • the stomach cancer may include both primary and metachronous stomach cancer, and accordingly, not only can the occurrence of stomach cancer be diagnosed and predicted even in normal people with a family history or risk factors, but also metachronous stomach cancer can be predicted. .
  • MMC Metalchronous Gastric Cancer
  • the present invention relates to early gastric cancer patients treated with endoscopic submucosal dissection, comprising an agent for measuring the level of mRNA or protein expressed therefrom of any one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2.
  • an agent for measuring the level of mRNA or protein expressed therefrom of any one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2. Provides a composition for predicting prognosis.
  • endoscopic submucosal dissection refers to a procedure for removing gastric polyps, adenomas, and early gastric cancer without lymph node metastasis using an endoscopic device.
  • the expression of CDK1, KDF1, CREB5, or AKT2 is confirmed in patients with early gastric cancer treated with endoscopic submucosal dissection to predict the possibility of developing metachronous gastric cancer, and through this, the possibility of developing metachronous gastric cancer is predicted after endoscopic submucosal dissection treatment. It was confirmed that the prognosis of stomach cancer patients can be predicted.
  • the present invention provides a use for predicting the possibility of developing gastric cancer of a composition
  • a composition comprising an agent for measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CREB5 and AKT2.
  • the present invention provides the use of an agent for measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CREB5 and AKT2 for preparing an agent for predicting the possibility of developing gastric cancer.
  • the present invention provides a use for predicting the possibility of developing metachronous gastric cancer of a composition comprising an agent for measuring the level of mRNA or protein expressed therefrom of any one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2. to provide.
  • the present invention provides an agent for measuring the level of mRNA or protein expressed therefrom of any one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2 for producing an agent for predicting the possibility of developing metachronous gastric cancer. Provides a purpose.
  • the present invention provides an early stage treated with endoscopic submucosal dissection of a composition comprising an agent for measuring the level of mRNA or protein expressed therefrom of any one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2. It is used to predict the prognosis of stomach cancer patients.
  • the present invention provides the mRNA of one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2 or the protein expressed therefrom for producing an agent for predicting the prognosis of patients with early gastric cancer treated with endoscopic submucosal dissection. Provides the use of preparations to measure levels.
  • the present invention provides a kit for predicting the likelihood of developing gastric cancer or metachronous gastric cancer, comprising the composition.
  • the “kit” includes an agent for measuring the mRNA or protein of one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2, thereby reducing the possibility of developing gastric cancer or metachronous gastric cancer. It refers to a tool that allows prediction.
  • the kit includes a reverse transcription polymerase chain reaction (RT-PCR) kit, a real-time polymerase chain reaction (qRT-PCR) kit, a DNA chip kit, an enzyme-linked immunosorbent assay (ELISA) kit, and a protein chip kit. It may be one or more selected from the group consisting of, but is not limited thereto.
  • the kit of the present invention may include other components, compositions, solutions, devices, etc. commonly required for these detection methods.
  • the substance that detects the expression level of the mRNA or protein can be applied at any number of times, one or more times, and there is no limit to the order or follow-up of applying each substance, and the application of each substance may be carried out simultaneously or in advance. there is.
  • the kit for measuring the mRNA expression level of the gene of the present invention may be a kit containing the essential elements required to perform RT-PCR.
  • the RT-PCR kit consists of test tubes or other suitable containers, reaction buffer (of varying pH and magnesium concentration), deoxynucleotides (dNTPs), Taq-polymerase and reverse transcriptase, in addition to each primer pair specific for the gene. It may include enzymes such as DNase, RNAse inhibitors, DEPC-water, sterilized water, etc. Additionally, it may include a pair of primers specific to the gene used as a quantitative control.
  • kits of the present invention may include essential elements required to perform DNA chip analysis.
  • a kit for DNA chip analysis may include a substrate to which a cDNA corresponding to a gene or a fragment thereof is attached as a probe, and reagents, agents, enzymes, etc. for producing a fluorescent label probe. Additionally, the substrate may include cDNA corresponding to a quantitative control gene or a fragment thereof.
  • the kit of the present invention can be a protein chip analysis kit for measuring the level of the protein encoded by the gene.
  • the kit is not particularly limited thereto, but includes a base material, a suitable buffer solution, and a suitable buffer solution for immunological detection of antibodies. , secondary antibodies labeled with chromogenic enzymes or fluorescent substances, chromogenic substrates, etc.
  • the substrate is not particularly limited thereto, but nitrocellulose membranes, 96 well plates synthesized from polyvinyl resin, 96 well plates synthesized from polystyrene resin, and glass slide glasses can be used, and the coloring enzyme is not particularly limited thereto.
  • peroxidase and alkaline phosphatase can be used
  • the fluorescent substance is not particularly limited thereto but can be FITC, RITC, etc.
  • the coloring substrate solution is not particularly limited thereto but ABTS (2, It can be 2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) or OPD (o-phenylenediamine) or TMB (tetramethyl benzidine).
  • the kit includes a container; directions; And it may include a detection agent for the mRNA or protein.
  • the container may serve to package the detection agent, and may also serve to store and secure the detection agent.
  • the material of the container may take the form of, for example, a bottle, a tub, a sachet, an envelope, a tube, an ampoule, etc., which may be partially or entirely made of plastic, glass, paper, or foil. , wax, etc.
  • the container may be equipped with a completely or partially removable closure that may initially be part of the container or may be attached to the container by mechanical, adhesive, or other means, and may also provide access to the contents by needle. A stopper can be installed.
  • the kit may include an external package, and the external package may include instructions for use of the components.
  • the present invention includes the steps of (a) measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CREB5 and AKT2 in a biological sample isolated from a subject; and
  • the gastric cancer may include metachronous gastric cancer, and the method is a method of extracting the mRNA of one or more genes selected from the group consisting of CDK1 and KDF1 or the protein expressed therefrom in a biological sample isolated from a subject. It may further include, but is not limited to, measuring the level and comparing it with the level measured in a sample separated from the control group.
  • the present invention includes the steps of (a) measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2 in a biological sample isolated from a subject; and
  • the present invention provides the step of (a) measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2 in a biological sample isolated from an early gastric cancer patient. ; and
  • the mRNA level of the gene is measured using reverse transcription polymerase chain reaction (RT-PCR), competitive reverse transcription polymerase chain reaction (competitive RT-PCR), real time quantitative RT-PCR, Multiplex reverse transcription polymerase chain reaction (Multi-plex PCR), real-time polymerase chain reaction (qRT-PCR), RNase protection method, Northern blotting, DNA chip technology assay ), Methylated DNA binding domain sequencing (MBD-seq) analysis method, and Reduced representation bisulfite sequencing (RRBS) analysis method.
  • RT-PCR reverse transcription polymerase chain reaction
  • competitive RT-PCR competitive reverse transcription polymerase chain reaction
  • Real time quantitative RT-PCR Multiplex reverse transcription polymerase chain reaction
  • Multi-plex PCR Multiplex reverse transcription polymerase chain reaction
  • qRT-PCR real-time polymerase chain reaction
  • RNase protection method RNase protection method
  • Northern blotting DNA chip technology assay
  • MBD-seq Methylated DNA binding domain sequencing
  • RRBS Reduced representation
  • the composition can analyze the expression level of four genes at once through multiplex reverse transcriptase polymerase reaction (Multi-plex PCR), but is not limited thereto.
  • Multi-plex PCR multiplex reverse transcriptase polymerase reaction
  • the protein level is measured by Western blot, enzyme linked immunosorbent assay (ELISA), radioimmunoassay (RIA), radioimmunodiffusion, and Ouchterlony.
  • Immunodiffusion rocket immunoelectrophoresis, Immunohistochemistry (IHC), Immunoprecipitation Assay, Complement Fixation Assay, Fluorescence Activated Cell Sorter (FACS), and It may be measured by one or more methods selected from the group consisting of protein chips, but is not limited thereto.
  • the mRNA level or protein level of the gene can be measured using a single biological sample, but is not limited thereto.
  • the biological sample refers to any sample that can confirm the presence or expression level of mRNA or protein of CDK1, KDF1, CREB5, or AKT2 in the body, such as tissue, cells, or tissue isolated from a subject, It may be one or more selected from the group consisting of whole blood, serum, plasma, saliva, sputum, cerebrospinal fluid, urine, and feces, but is not limited thereto.
  • tissue may be gastric mucosa (GM) tissue or intestinal metaplasia (IM) tissue, but is not limited thereto.
  • the information provision method for predicting the possibility of developing gastric cancer or metachronous gastric cancer is (c) the level of the mRNA or protein measured in a biological sample isolated from a subject is measured in a biological sample isolated from the control group. If it is higher than the level, a step of determining that the risk of developing gastric cancer or metachronous gastric cancer is high may be further included, but is not limited to this.
  • the method of providing information for predicting the prognosis after endoscopic submucosal dissection treatment of patients with early gastric cancer is (c) the level of the mRNA or protein measured in the biological sample isolated from the early gastric cancer patient is measured in the biological sample isolated from the control group. If it is higher than the level measured in , a step of predicting that the prognosis will be poor after endoscopic submucosal dissection treatment may be further included, but is not limited to this.
  • the biological sample may be gastric mucosal tissue surrounding the tumor of a patient with early gastric cancer, and may be separated regardless of before, after, or elapsed time of endoscopic submucosal dissection treatment, but is not limited thereto.
  • the present invention includes the steps of (a) preparing an agent for measuring the level of mRNA or protein expressed therefrom of one or more genes selected from the group consisting of CREB5 and AKT2;
  • the present invention includes the steps of (a) preparing an agent for measuring the level of mRNA or protein expressed therefrom of any one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2;
  • the present invention includes the steps of (a) preparing an agent for measuring the level of mRNA or protein expressed therefrom of any one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2;
  • (c) providing a method for predicting prognosis after endoscopic submucosal dissection treatment for patients with early gastric cancer, including the step of comparing the measured mRNA or protein level with the level measured in a biological sample isolated from the control group.
  • an agent for measuring the level of mRNA of the gene or protein expressed therefrom includes a primer or probe that specifically binds to the gene or mRNA; Alternatively, it may be an antibody or aptamer specific to the protein, but is not limited thereto.
  • prediction may mean confirming the possibility or risk of developing gastric cancer or metachronous gastric cancer for the purpose of the present invention, or confirming the prognosis after endoscopic submucosal dissection treatment for patients with early gastric cancer.
  • subject refers to a subject diagnosed with the onset of gastric cancer, recurrence of gastric cancer, or early gastric cancer, and for whom the possibility or prognosis of metachronous gastric cancer is to be predicted before or after endoscopic submucosal dissection treatment.
  • the subject or individual may include any animal that can develop stomach cancer, such as humans, dogs, horses, cows, rats, goats, rabbits, chickens, ducks, and geese, without limitation.
  • control group refers to both individuals who were not diagnosed with gastric cancer and individuals who were diagnosed with early gastric cancer and did not develop metachronous gastric cancer after treatment with endoscopic submucosal dissection.
  • the possibility of developing gastric cancer in a subject can be predicted by comparing a sample isolated from an individual not diagnosed with gastric cancer with a sample isolated from a subject for whom the possibility of developing gastric cancer is to be predicted, and the possibility of developing gastric cancer in the subject can be predicted after endoscopic submucosal dissection treatment.
  • the possibility of developing metachronous gastric cancer in a subject can be predicted by comparing a sample isolated from an individual who has not developed metachronous gastric cancer with a sample isolated from a subject for whom the possibility of developing metachronous gastric cancer is to be predicted.
  • the method of providing information for predicting the possibility of developing gastric cancer of the present invention is a single sample collection method, instead of the existing method of collecting samples from an individual multiple times to measure the expression level of the above four genes. It can be measured using a sample, and diagnosis and prediction of gastric cancer can be made with just one measurement by measuring gene expression levels using a multiplex reverse transcriptase polymerase reaction.
  • the above method not only makes it possible to predict metachronous gastric cancer, but can also be useful in predicting the risk of developing gastric cancer in normal people.
  • Example 1 Selection of candidate genes for diagnosing and predicting the occurrence of gastric cancer
  • RNA sequencing was performed on normal gastric mucosal tissue stored in an ultra-low temperature freezer at the time of diagnosis to identify differentially expressed genes (DEGs).
  • DEGs differentially expressed genes
  • correlation analysis was performed based on gene expression level, number of metachronous gastric cancers, number of adenomas, atrophic gastritis, and degree of intestinal metaplasia, and self-organizing map (SOM) analysis and isoform analysis were performed. Then, candidate genes were selected.
  • SOM self-organizing map
  • an effectiveness evaluation set consisting of 50 subjects who developed metachronous gastric cancer after endoscopic submucosal dissection treatment and 100 subjects who did not develop metachronous gastric cancer was constructed independently of the 46 subjects mentioned above, and real-time qPCR, Western blot and immunohistochemistry were performed and compared.
  • RNA sequencing was performed on normal gastric mucosal tissue stored in an ultra-low temperature freezer, and differentially expressed genes (DEGs) were identified using DESeq2.
  • DEGs differentially expressed genes
  • the number of metachronous gastric cancers, number of adenomas, neoplasms (gastric cancer + adenomas), degree of atrophic gastritis (OLGA stage), degree of intestinal metaplasia (OLGMI stage) and DESeq2 were used. Correlation analysis was performed between the expression levels of each identified gene, and self-organizing map (SOM) and alternative splicing analysis were performed.
  • SOM self-organizing map
  • Example 2 Target gene selection and protein expression confirmation by confirming the expression level of candidate genes in gastric cancer cell lines
  • Candidate genes selected through RNA sequencing performed on normal gastric mucosa tissue around the tumor and candidate genes selected by WES of the tumor were targeted in various gastric cancer cell lines (long type: SNU216, MKN1, AGS, diffuse type: SNU1, SNU5, SNU16, SNU488). , SNU601, SNU620, SNU638, MKN45) and normal gastric mucosal cell lines (HFE145), the gene expression levels were compared by performing real-time polymerase chain reaction (qRT-PCR).
  • proteins were isolated from the tissues of some patients, and the protein expression levels of CDK1 and KDF1, which were highly expressed in the mGC group, were confirmed through Western blot.
  • KDF1 expression was higher in the tissues of subjects who developed metachronous gastric cancer compared to the tissues of subjects who did not develop metachronous gastric cancer ( bottom of Figure 4b).
  • an effectiveness evaluation set independent of the 46 patients selected for candidate gene selection was constructed.
  • the set consists of 50 subjects who developed metachronous gastric cancer after endoscopic submucosal dissection treatment and 100 subjects who did not, and were also selected by matching age, gender, and H. pylori infection status.
  • the accuracy of the CDK1 ROC curve analysis was AUC 0.829
  • the KDF1 ROC curve analysis result showed AUC of 0.841
  • the AUC of the AKT2-isoform ROC curve was 0.771, confirming that the accuracy of each gene for gastric cancer prediction is high. I was able to.
  • OLGIM stage the degree and scope of atrophy is evaluated and divided into five stages (stage 0-IV), and it has been reported in several studies that it is used as an indicator to predict the possibility of developing gastric cancer along with the OLGA stage.
  • CDK1, KDF1, CREB5, and AKT2 isoforms can be used as predictors of gastric cancer. As the expression of these genes increases, they can be used as markers to predict the occurrence of metachronous gastric cancer or primary gastric cancer. .
  • the prediction of the possibility of developing stomach cancer according to the present invention can be confirmed with a single tissue sample, and the technical advantage is that it is highly useful because it is possible to predict the possibility of developing stomach cancer with a single measurement method using multi-plex PCR, etc. there is.
  • it includes a method to quantify basal gastritis in a quantitative way that can predict the development of gastric cancer not only in metachronous gastric cancer but also in normal people, so it is possible to predict the risk of gastric cancer in normal people with a family history of gastric cancer or risk factors. provided at the same time.
  • the patient's prognosis after endoscopic submucosal dissection can be predicted.
  • Any one or more genes selected from the group consisting of CDK1, KDF1, CREB5, and AKT2 according to the present invention are useful for predicting the possibility of developing gastric cancer or metachronous gastric cancer, or predicting prognosis in patients with early gastric cancer treated with endoscopic submucosal dissection. It is expected that it can be used, and there is potential for industrial use.

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Abstract

La présente invention concerne un biomarqueur permettant de prédire la probabilité de développer un cancer gastrique et son utilisation. En mesurant le niveau d'ARNm d'au moins un gène choisi dans le groupe constitué de CDK1, KDF1, CREB5 et AKT2 ou le niveau d'une protéine exprimée à partir de ce gène, il est possible de prédire la probabilité de développer un cancer gastrique, y compris un cancer gastrique métachrone. Une composition pour prédire la probabilité de développer un cancer gastrique, selon la présente invention, présente non seulement une grande précision dans la prédiction de l'apparition du cancer gastrique, mais permet également la prédiction du cancer gastrique par un procédé de mesure unique en utilisant la PCR multiplex avec un seul échantillon tissulaire, et est donc très utilisable. En outre, étant donné qu'un procédé quantitatif de prédiction de l'apparition du cancer gastrique ainsi que du cancer gastrique métachrone comprend un procédé de quantification de la gastrite basale, La présente est un procédé de prédiction du risque de développer un cancer gastrique chez des individus normaux ayant des antécédents familiaux de cancer gastrique ou des facteurs de risque. En outre, il est possible de prédire le pronostic des patients en prédisant l'apparition d'un cancer gastrique métachrone chez les patients atteints d'un cancer gastrique précoce traités par dissection sous-muqueuse endoscopique.
PCT/KR2022/014463 2022-05-31 2022-09-27 Biomarqueur pour prédire la probabilité de développer un cancer gastrique et son utilisation WO2023234485A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20120065959A (ko) * 2010-12-13 2012-06-21 사회복지법인 삼성생명공익재단 위암의 예후 예측용 마커 및 이를 이용하는 위암의 예후 예측 방법
WO2020226333A1 (fr) * 2019-05-03 2020-11-12 주식회사 디시젠 Méthode de prédiction et de pronostic du cancer et composition à cet effet
CN113555121A (zh) * 2021-08-25 2021-10-26 南方医科大学南方医院 一种胃癌预后标志物的筛选和分类方法、胃癌预后标志物和检测胃癌预后的试剂及应用

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102253304B1 (ko) 2019-11-28 2021-05-20 경상국립대학교산학협력단 위암 재발 예측용 바이오 마커

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20120065959A (ko) * 2010-12-13 2012-06-21 사회복지법인 삼성생명공익재단 위암의 예후 예측용 마커 및 이를 이용하는 위암의 예후 예측 방법
WO2020226333A1 (fr) * 2019-05-03 2020-11-12 주식회사 디시젠 Méthode de prédiction et de pronostic du cancer et composition à cet effet
CN113555121A (zh) * 2021-08-25 2021-10-26 南方医科大学南方医院 一种胃癌预后标志物的筛选和分类方法、胃癌预后标志物和检测胃癌预后的试剂及应用

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BOKYUNG KIM, JUNGMIN CHOI, HARIM CHUN, MIREE PARK, SEUNGKYUNG KANG, EUNWOO LEE, HAN MYUNG LEE, HYUNSOO CHUNG, SANG GYUN KIM, SOO-J: "FP19-04: KDF1 and CDK1 are Candidate Markers for Prediction of Metachronous Gastric Cancer Development in Patients with Early Gastric Cancer Treated Endoscopic Submucosal Dissection", GUT AND LIVER, GUT AND LIVER, EDITORIAL OFFICE, KR, vol. 15, no. 6, Suppl. 1, 18 November 2021 (2021-11-18) - 20 November 2021 (2021-11-20), KR , pages 44, XP009551519, ISSN: 1976-2283 *
JIRO WATARI; , KENTARO MORIICHI; , HIROKI TANABE; SHIN KASHIMA; YOSHIKI NOMURA; MIKIHIRO FUJIYA; TOSHIHIKO TOMITA; TADAYUKI OSHIMA: "Biomarkers predicting development of metachronous gastric cancer after endoscopic resection: an analysis of molecular pathology of Helicobacter pylori eradication", INTERNATIONAL JOURNAL OF CANCER, JOHN WILEY & SONS, INC., US, vol. 130, no. 10, 24 August 2011 (2011-08-24), US , pages 2349 - 2358, XP071286894, ISSN: 0020-7136, DOI: 10.1002/ijc.26275 *
KIM, B.: "Candidate Gene Identification for Prediction of Metachronous Gastric Cancer Development using RNA Sequencing in Patients with Early Gastric Cancer Treated with Endoscopic Submucosal Dissection", KOREA INTERNATIONAL GASTRIC CANCER WEEK 2021 VIRTUAL CONFERENCE, P-067, 30 September 2021 (2021-09-30) *
WEI KANG;JOANNA HM TONG;RAYMOND WM LUNG;YUJUAN DONG;WEIQIN YANG;YI PAN;KIN MANG LAU;JUN YU;ALFRED SL CHENG;KA FAI TO: "let-7b/g silencing activates AKT signaling to promote gastric carcinogenesis", JOURNAL OF TRANSLATIONAL MEDICINE, BIOMED CENTRAL, vol. 12, no. 1, 5 October 2014 (2014-10-05), pages 281, XP021200372, ISSN: 1479-5876, DOI: 10.1186/s12967-014-0281-3 *

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